We have studied the phosphorylation system associated with the rat cerebrocortical microtubule fraction after short- and long-term administration (15 mg/kg) of fluvoxamine, a selective serotonin reuptake inhibitor with antidepressant activity. Fluvoxamine administered for 5 days significantly enhanced the 32P incorporation stimulated by cAMP into MAP2, while it failed to produce this effect after 12 and 21 days. Moreover, in the same periods of treatment no changes were observed in basal phosphorylation and in the pattern of microtubule proteins. In conclusion, our results suggest that changes in the protein phosphorylation system associated with the microtubule fraction could represent an early neurochemical modification involved in the action of fluvoxamine.